Kurtz T W, Morris R C
Hypertension. 1987 Jul;10(1):127-31. doi: 10.1161/01.hyp.10.1.127.
The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension. As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY). But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain. It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred. Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions. We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure. Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6 generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain. Thus, interpretation of studies employing "the Wistar-Kyoto rat strain" as a control for the SHR may be much more problematic than has previously been recognized.
最初在京都培育的自发性高血压大鼠(SHR)是研究最为广泛的原发性高血压动物模型。作为SHR的对照,大多数研究人员使用了来自京都的Wistar大鼠群体中血压正常的后代(Wistar-京都大鼠,WKY),该群体正是SHR品系的来源。但是,认为WKY可作为SHR有效对照的假设基于一个默认前提,即所有WKY构成一个单一的近交系。然而,美国国立卫生研究院在SHR完全近交后(即经过20代兄妹交配后)才分发其种畜,而WKY的种畜在完全近交之前就已分发。因此,WKY的生物学变异性可能大于SHR。为了探究这种可能性,我们从美国两家最大的商业供应商处获取了SHR和WKY,并在相同的身体和代谢条件下系统地测量了这些大鼠的生长速率和血压。我们发现,来自一个供应商的WKY在生长速率和血压方面均与另一个供应商的不同。相比之下,来自两家供应商的SHR在生长速率或血压方面并无差异。由于美国国立卫生研究院可能早在F6代就分发了WKY的种畜,所以目前被指定为WKY的大鼠有可能并不构成一个单一的近交系。因此,将“Wistar-京都大鼠品系”作为SHR对照的研究的解释可能比之前所认识到的问题要大得多。